The preparation of pharmaceutical compositions requires a suitable solvent or carrier system for dispersing the pharmaceutically active substance so that the composition can be administered to a patient. The solvent must be able to solve or dissolve a therapeutically effective amount of the active substance to provide an active composition. However, many pharmaceutically active compositions are not sufficiently soluble in solvents, such as in water. Another problem is that many pharmaceutical active substances become unstable when diluting them for an infusion solution or they exhibit decomposition or loss of activity of the active substance during storage in a solvent system. The poor solubility and the susceptibility to decomposition highly limit the use of these pharmaceutically active substances, which are poorly soluble in water, in therapy.
Most of the currently available dosage forms of the pharmaceutically active substance 7β-hydroxycholesterol are capsules for oral administration because 7β-hydroxycholesterol is insoluble in water.
However, there is an approach for the preparation of 7β-hydroxycholesterol in a water soluble form. The application DE 35 07 721 A1 describes a method for the preparation of water soluble derivatives of 7β-hydroxycholesterol. The reaction of 7β-hydroxycholesterol with succinic anhydride has been carried out in order to render the derivatives water soluble, and the sodium or potassium salt has been formed from the resulting hemisuccinate.
Christ et al. (Anticancer Res. 1991, 11(1): 359-64) describe the preparation of phosphodiesters of 7β-hydroxycholesterol. These two salts exhibit an antitumor activity and are water soluble, however, are disadvantageous in that they do not remain stable in an aqueous solution.
The application EP 0 007 834 A1 relates to water soluble derivatives of cholesterol, particularly water soluble derivatives of 7β-hydroxycholesterol. This is achieved by compounds and complexes of albumin with organic dibasic half-esters of 7β-hydroxycholesterol.
The application EP 2 522 350 A1 relates to the use of an active substance combination consisting of an derivative of 1-diethylaminoethyl-3-chinoxalin-2-on and an oxysterol for the suppression of resistances in the treatment of cancer and for the enhancement of the immuno-potential in cancer, bacterial and viral diseases, autoimmune diseases, enhanced stress loading and environmental pollution.
Larsson et al., Free Radical Biology & Medicine 43 (2007), pp. 695-701 describes the conversion of 7β-hydroxycholesterol and 7-ketocholesterol in vivo, wherein both of which are surrogate markers for oxidative stress.
A disadvantage of the prior art is that the signal substance 7β-hydroxycholesterol that is produced in the body could not be used in an aqueous solution until now, but only two water soluble salts thereof (hydroxycholesteryl-bishemisuccinate-diethanolamine and 7β-hydroxycholesteryl-bishemisuccinate-disodium). Thus, Maier et al. (Anticancer Res. 1999, 19(5b), pp. 4251-4256) describe the induction of apoptosis by these two salts in human cell lines of colon carcinoma. These two salts are water soluble, however, are instable in an aqueous solution. After several hours, the substance starts to decompose and to flocculate. Furthermore, the way how the bishemisuccinate is acting in contrast to 7β-hydroxycholesterol and which are the additional side effects of ethanolamine upon administration to the human are not known.
Another disadvantage of the prior art is that 7β-hydroxycholesterol in oral form shall not be used because it is not known how much of the substance gets to the target site. Moreover, the absorption of 7β-hydroxycholesterol by the gastrointestinal tract is not known.